The challenges of real-time Gamma Knife inverse planning are the large number of variables involved and the unknown search space a priori. With limited collimator sizes, shots have to be heavily overlapped to form a smooth prescription isodose line that conforms to the irregular target shape. Such overlaps greatly influence the total number of shots per plan, making pre-determination of the total number of shots impractical. However, this total number of shots usually defines the search space, a pre-requisite for most of the optimization methods. Since each shot only covers part of the target, a collection of shots in different locations and various collimator sizes selected makes up the global dose distribution that conforms to the target. Hence, planning or placing these shots is a combinatorial optimization process that is computationally expensive by nature. We have previously developed a theory of shot placement and optimization based on skeletonization. The real-time inverse planning process, reported in this paper, is an expansion and the clinical implementation of this theory. The complete planning process consists of two steps. The first step is to determine an optimal number of shots including locations and sizes and to assign initial collimator size to each of the shots. The second step is to fine-tune the weights using a linear-programming technique. The objective function is to minimize the total dose to the target boundary (i.e., maximize the dose conformity). Results of an ellipsoid test target and ten clinical cases are presented. The clinical cases are also compared with physician's manual plans. The target coverage is more than 99% for manual plans and 97% for all the inverse plans. The RTOG PITV conformity indices for the manual plans are between 1.16 and 3.46, compared to 1.36 to 2.4 for the inverse plans. All the inverse plans are generated in less than 2 min, making real-time inverse planning a reality.